PROJECT SUMMARY Ultima Genomics, Inc. proposes to develop a novel sequencing-by-synthesis (SBS) chemistry that will further leverage the strengths of the company's high-throughput sequencing system. The new technology will further reduce cost compared with state-of-the-art commercial technologies and will particularly benefit DNA sequencing applications that are cost constrained, such as sequencing large populations, generating methylation and transcriptome profiles for millions of single cells, and enabling liquid biopsy applications. Target customers include genome centers, CROs, research labs, and clinical labs. The company is pioneering a series of inter-related innovations that mutually reinforce one another in a virtuous circle to achieve much lower cost. The first generation of this platform ? which is currently under development and will soon be seeded to select beta test sites ? substantially advances the state of the art, but does not exploit the full potential of the innovations. In the proposed Direct to Phase 2 project, the company will design, develop, and optimize a new chemistry that unlocks the full potential of the platform; port the new chemistry to the existing hardware platform while maintaining highly competitive specifications for accuracy, read length, and time to answer; demonstrate the throughput improvements that will further lower overall costs; and rigorously validate performance across these and other metrics. By dramatically reducing sequencing cost, Ultima Genomics' technology will directly impact a wide range of scientific capabilities with direct relevance for public health, including characterization of tumors, detection of early stage cancers through blood test, and personalized/precision medicine.